We propose to carry out two sets of structural studies. The first involves studies on T. aquaticus DNA depdendent DNA polymerase I (TaqP) and its complexes with substrates, including primer/template oligonucleotides. The second set involves studies on Fab fragments of antibodies directed against TaqP and their complexes with antigenic peptides. Studies on TaqP will contribute towards understanding of structural bases of DNA replication, structural underpinnings of PCR as well as provide a model system for evaluation of DNA polymerase inhibitors as potential drug candidates for treatment of viral infections and cancer. Studies of Fab-peptide complexes will contribute towards making PCR less noisy and more selective towards targeted DNA. We deem synchrotron radiation to be essential to enable us to measure data to high enough resolution and with sufficient precision to permit us to obtain biologically meaningful results on both sets of studies.